Study of the Role of the Tumor Microbiota in the Neoadjuvant Therapy Response on Triple Negative Breast Cancer Patients

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by the negligible expression of estrogen, progesterone, and HER2 receptors. Compared with other breast cancer subtypes, TNBC has historically had more limited therapeutic options and is associated with a heterogeneous clinical course and a variable response to treatment. Evidence shows that the introduction of combined chemotherapy and immunotherapy in the neoadjuvant treatment setting has improved the rate of pathological complete response (pCR) in patients with TNBC. However, not all patients benefit equally from treatment, and a substantial proportion of patients do not achieve pCR.

Identifying biological factors that contribute to this variability is therefore important to improve patient stratification and to recognize predictive biomarkers for treatment response.

Increasing evidence indicates that the microbiota may play an important role in regulating the response to anticancer treatment, by modulating the activity of the host immune system.

In several tumor types, such as melanoma, non-small cells lung carcinoma (NSCLC) and colorectal carcinoma (CRC), composition and functional activity of the intestinal microbiota have been associated with the efficacy of chemotherapy and immune checkpoint-based treatments. Specifically, the intestinal microbiota can influence systemic immune activity through interactions with immune cells, microbial metabolites and inflammatory pathways. Additionally, the tumor itself also contains a distinct microbial community. Tumor-associated microorganisms may interact directly with tumor cells and influence inflammatory signaling, antigen presentation, immune cell recruitment, and the functional state of immune cells. These processes can contribute to the composition and activity of the tumor immune microenvironment (TIME), which is an important determinant of tumor progression and response to systemic therapy. Hence, alterations in the composition of the microbiota may contribute to either an immune-permissive or an immunosuppressive tumor environment, influencing the ability of the tumor to respond to neoadjuvant therapy.

Consequently, the relationship between the intestinal microbiota, intratumoral microbiota and TIME emerges as a promising area of investigation in TNBC.